Daptomycin is a lipopeptide antibiotic represented by the following structural formula (I)
and is described, for example, in U.S. Pat. No. 4,537,717, the contents of which are incorporated herein by reference.
Daptomycin is used in the treatment of Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-susceptible Staphylococcus aureus (MSSA), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subspecies equisimilis, and Enterococcus faecalis (vancomycin-susceptible isolates only) in complicated skin infections and bloodstream infections (bacteremia), including right-sided infective endocarditis. Daptomycin is commercially available as Cubicin™ for intravenous administration.
Daptomycin exhibits premature degradation upon reconstitution of the lyophilized product. The reconstituted daptomycin exhibits increased degradation after reconstitution and is, therefore, not suitable for long-term storage in liquid form. Some of the main degradants of daptomycin are the hydrolysis product of daptomycin, the β-isomer of daptomycin and anhydro daptomycin. The hydrolysis product (ring opening compound) appears as the main impurity at a Relative Retention Time (RRT) of about 0.66, the β-isomer of daptomycin appears as the main impurity at an RRT of about 0.97 and anhydro daptomycin appears as the main impurity at an RRT of about 1.1. There is a need for daptomycin formulations with increased stability.